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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 379 records · Page 21Linked to original sources
PubMed1983

A facile synthesis of bestatin.

Bestatin, an immunomodulator useful in cancer treatment with the structure: N-[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, has been synthesized from N-acyl-alpha-aminoacetophenone. This novel method using readily available reagents and mild conditions can be applied to a large scale production of this useful agent. The overall yield of bestatin was 10.5% from N-acetyl-alpha-aminoacetophenone and 7.8% from N-benzoyl-alpha-aminoacetophenone.

Adjuvants, Immunologic↗
PubMed1983

Abnormalities of various serum enzyme activities in patients with congenital adrenal hyperplasia.

Recently, attentions are being aroused as to the enzymatic network abnormalities lying behind congenital enzyme deficiency syndromes. We investigated abnormalities in activities of various hydrolytic enzymes in serum of patients with congenital adrenal hyperplasia (CAH, 21-hydroxylase deficiency). Several enzyme activities including trypsin-like enzyme, cathepsin C and esterase were significantly decreased in patients' serum. Especially the esterase activity in patients' serum was reduced to one third of controls and this may have some relations to the abnormal steroid metabolism of these patients. A multivariate analysis showed unexpectedly extensive abnormalities in enzyme interrelationships. These results suggest that wide variety of abnormal metabolism may be related to an apparent enzyme deficiency.

Adolescent↗
PubMed1982

The effects of lactoyl-pepstatin and the pepsin inhibitor peptide on pig cathepsin D.

Lactoyl-pepstatin (an acylated tetrapeptide) is much more readily soluble in aqueous media than the more common isovaleryl- and acetyl-pepstatins (acylated pentapeptides). However, the K1 value for inhibition of cathepsin D by lactoyl-pepstatin at pH 3.5 is approx. 10(-7) M, some two to three orders of magnitude weaker than has been obtained previously for isovaleryl- or acetyl-pepstatins. One of the peptides released during activation of pig pepsinogen is known to be an effective inhibitor of pig pepsin, but it does not alter the activity of the similar aspartic proteinase, pig cathepsin D.

Animals↗
PubMed1982

Relationship between enhancement of morphine analgesia and inhibition of enkephalinase by 2S, 3R 3-amino-2-hydroxy-4-phenylbutanoic acid derivatives.

The effects of nineteen AHPA* derivatives were examined on morphine analgesia by tail-flick test in rats and on enkephalinase inhibition which was based on the formation of tyrosyl-glycyl-glycine from met-enkephalin. The correlation between the enhancement of morphine analgesia in vivo and enkephalinase inhibition in vitro was analyzed. The different analogs varied considerably in the degree of enhancement of morphine analgesia and inhibition of enkephalinase. A close relationship between enkephalinase inhibition expressed by IC50 in vitro and enhancement of morphine analgesia in vivo was observed in thirteen out of nineteen AHPA derivatives examined. One of other six AHPA derivatives which showed weak effectiveness in potentiating on morphine analgesia but was highly potent as an enkephalinase inhibitor, caused potent analgesic action when it was applied intracisternally indicating poor penetration of the blood brain barrier. The possibility was discussed that some of other compounds excluded from the linear relationship might act on other enkephalin degrading enzymes such as aminopeptidase.

Aminopeptidases↗
PubMed1982

Pig skin epidermal calmodulin: effect on calmodulin deficient phosphodiesterase.

Calmodulin, a calcium-dependent modulator protein, is known to mediate a great number of Ca++-dependent processes in various tissues. Although it was originally described as a protein activator of cyclic nucleotide phosphodiesterase, the sensitivity of phosphodiesterases to this compound are suggested to be variable from tissue to tissue. In order to determine whether there was calmodulin-like activity in pig skin epidermis and to see its relationship to epidermal phosphodiesterase, we used an established calmodulin deficient phosphodiesterase system prepared from bovine heart. Calmodulin deficient phosphodiesterase prepared from bovine heart was markedly stimulated by the addition of pig skin (epidermal) boiled extract in the presence of calcium. Boiled skin extract alone had only little phosphodiesterase activity by itself. This effect of boiled skin extract on bovine heart phosphodiesterase was inhibited by the addition of EGTA, a divalent metal ion chelator of relative Ca++ specificity. At a fixed concentration of EGTA, increasing the Ca++ concentration counteracted the effect of EGTA. Pure pig skin epidermis (separated by trypsinization, NaBr, CaCl2-sucrose or NH4Cl treatment) was also shown to have heat-stable calmodulin activity. In contrast to the bovine heart phosphodiesterase, epidermal phosphodiesterase was only partially inhibited when Ca++ was removed by EGTA. The addition of boiled skin extract on the crude extract of epidermal phosphodiesterase had minimal effect on the enzyme activity. Overall results indicate that although pig skin epidermis contains significant amount of calmodulin, the regulation of phosphodiesterase may not be the main biological activity of epidermal calmodulin.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1982

Epidermal surface receptors which link pharmacological mediators to the adenylate cyclase system.

The major purpose of our studies has been to investigate various stimulators of the epidermal adenylate cyclase system. We have recognized the occurrence of four distinct adenylate cyclase systems which respond respectively to catecholamine, histamine, prostaglandin and adenosine. The exposure of floating skin slices in vitro to a stimulator causes a rapid intracellular accumulation of cyclic AMP, which is always transient. Further addition of the same stimulator will not stimulate the same receptor system against the state of 'refractoriness'. The addition of any of the other stimulators can increase the cyclic AMP level. Furthermore, the fact that each stimulator can yield an 'additive' stimulatory effects leads to the conclusion that the epidermis has four distinctly specific and independent adenylate cyclase systems. Our recent investigations have been directed to the analyses of subunits of these skin surface receptor-adenylate cyclase systems. We used two experimental systems, i.e. one being a 'leaky' cell system in which its subunits such as receptor, GTP-regulatory protein and the catalytic unit (adenylate cyclase) are still linked together, and the other being independent preparations of the receptor and catalytic units (with GTP-regulatory protein). These systems allowed us to probe the cell membrane from the inside as well as from the outside. Some of the preliminary kinetic data are herein introduced.

Adenylyl Cyclases↗
PubMed1982

Studies on effects of forphenicinol on immune responses.

The oral administration of forphenicinol, S-2-(3-hydroxy-4-hydroxymethylphenyl)glycine which was synthesized during the study of derivatives and analogs of forphenicine, augmented delayed-type hypersensitivity to sheep red blood cells and oxazolone in mice. The treatment with forphenicinol restored DTH in mice immuno-suppressed by cyclophosphamide to normal response. Forphenicinol neither augmented antibody-formation nor stimulated proliferation of lymphocytes in the presence or absence of lectins. Phagocytosis by peritoneal macrophages was enhanced by forphenicinol in vivo and in vitro. Forphenicinol was effective in increasing the production of CFU-C in the presence of colony stimulating factor and partially prevented the reduction of leucocyte counts caused by mitomycin C.

Adjuvants, Immunologic↗
PubMed1982

Biosynthetic studies of ebelactone A and B by 13C NMR spectrometry.

Biosynthetic pathways of ebelactone A and B were studied by 13C NMR spectroscopy. By using 13C labeled compounds as precursors it was determined that ebelactone A was derived from one molecule of acetic acid and six propionic acids and ebelactone B from one molecule of acetic acid, five propionic acids and one butyric acid.

Animals↗
PubMed1981

Effects of trypsin on the cyclic AMP system of the pig skin.

Trypsin increased cyclic AMP levels of the pig skin. This effect was markedly potentiated by the cyclic nucleotide phosphodiesterase inhibitor theophylline. Without theophylline this trypsin-induced cyclic AMP accumulation was transient and the maximal accumulation was noted by 5 min. Soybean trypsin inhibitor inhibited this trypsin-induced cyclic AMP accumulation. After the trypsin treatment, marked acantholysis was noted histologically and the decreased responsiveness to other adenylate cyclase stimulators was seen. The decrease of the epinephrine response was most marked and that of histamine response was much less. Both low and high Km cyclic nucleotide phosphodiesterase activities were decreased by the trypsin treatment. However, at 5 min incubation time, when the increase in cyclic AMp level was most marked, the decrease in the phosphodiesterase activities was minimal. Trypsin seems to reveal its action through the proteolytic activation of adenylate cyclase system of the skin.

3',5'-Cyclic-AMP Phosphodiesterases↗